OVERALL DESCRIPTION (Adapted from the application) The Digestive Disease Center at Stanford University was established in 1987 and has two major areas of focus. The first deals with studying host-pathogen interactions, and the mechanism and signals that target leukocytes to specific digestive organs and pathogens. Infections under study include hepatitis A-D, H. pylori, and the diarrheal agents rotavirus, salmonella, E-coli, cholera and astrovirus. It also addresses mucosal immunity and targeting of immunocytes to the intestine and liver in normal and disease states including inflammatory bowel disease, viral hepatitis, and H. pylori-induced gastritis. The second focus addresses the cell and molecular biology of digestive epithelia with emphasis on normal and abnormal cell growth, differentiation, development, polarity, and the nature and role of signaling pathways and the cytoskeleton in facilitating these processes. This focus targets several digestive diseases including esophageal, pancreatic and colorectal cancer; cryptogenic liver disease; pancreatitis and Barrett?s esophagus. The Center consists of 29 established investigators who blend several clinical and basic science departments. Five core facilities are administered by the Center and they provide several important technologies and services. The Administrative Core offers the Pilot and Feasibility Program which provides one year funding ($20,000/year) to junior investigators or those with a collaborative project, the Named Investigator Program which provides a two year 20-25% effort/year support to a promising junior faculty, and a Collaborative Trainee Program that specifically funds trainees who work with two or more Center investigators. The Fluorescence Activated Cell Sorting/Immunoprobe Core offers an array of services that allow studying single cells. The Cell Imaging Core offers state of the art imaging tools including confocal and electron microscopy. The Microarray/DNA Sequencing Core offers the ability to identify disease-associated regulatory changes in multiple genes, and as such provides potential means to develop diagnostic and therapeutic modalities. Cell Biology & Signaling Core offers expertise and services in cell culture methods, characterizing protein-protein interaction, dissecting signaling pathway and characterizing regulatory modifications such as phosphorylation. In the aggregate, this Center brings together an accomplished group of investigators, creates a highly interactive environment, and makes available state of the art technologies to address important digestive diseases.